Tumor specific immunity is mediated by CTL that recognize peptide Ag in the context of MHC class I molecules and by Th cells that recognize peptide Ag in the context of MHC class II molecules. To clarify the relative importance of MHC class I and II Ag in tumor rejection, we transfected a K1735 melanoma that did not express constitutively either MHC class I or II Ag with H-2K(k) and/or I-A(k) genes and determined their tumorigenicity. K1735 transfectants expressing either K(k) or A(k) Ag alone produced tumors in normal C3H mice, whereas most transfectants that expressed both molecules were rejected in normal C3H mice but produced tumors in nude mice. However, the A(k) Ag requirement can be substituted by IL-2 because transfection of K(k)-positive/A(k)-negative K1735 cells with the IL-2 gene also resulted in abrogation of tumorigenicity in normal C3H mice but not in nude mice. Similarly, transfection of K(k)-negative/A(k)-positive K1735 cells with IFN- γ gene resulted in induction of MHC class I Ag as well as rejection of these tumors in normal C3H mice. The rejection of K1735 transfectants expressing K(k) and A(k) Ag in normal C3H mice required both CD4+ and CD8+ T cells. In addition, the transplantation immunity induced by K1735 transfectants expressing both K(k) and A(k) Ag completely cross-protected mice against challenge with K(k)-positive transfectants but only weakly protected them against challenge with parental K1735 cells or A(k)-positive transfectants. These results indicate that expression of either MHC class I or II Ag alone is insufficient to cause the rejection of K1735 melanoma in syngeneic hosts and that both Ag are necessary. In addition, our data suggest that the failure of K(k)-positive K1735 cells to induce a primary tumor rejection response in normal C3H mice may result from their inability to induce the helper arm of the antitumor immune response.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Immunology|
|State||Published - 1993|
ASJC Scopus subject areas
- Immunology and Allergy